Bone age assessment by multi-granularity and multi-attention feature encoding.

Background: Bone age assessment (BAA) is crucial for the diagnosis of growth disorders and the optimization of treatments. However, the random error caused by different observers' experiences and the low consistency of repeated assessments harms the quality of such assessments. Thus, automated assessment methods are needed. Methods: Previous research has sought to design localization modules in a strongly or weakly supervised fashion to aggregate part regions to better recognize subtle differences. Conversely, we sought to efficiently deliver information between multi-granularity regions for fine-grained feature learning and to directly model long-distance relationships for global understanding. The proposed method has been named the "Multi-Granularity and Multi-Attention Net (2M-Net)". Specifically, we first applied the jigsaw method to generate related tasks emphasizing regions with different granularities, and we then trained the model on these tasks using a hierarchical sharing mechanism. In effect, the training signals from the extra tasks created as an inductive bias, enabling 2M-Net to discover task relatedness without the need for annotations. Next, the self-attention mechanism acted as a plug-and-play module to effectively enhance the feature representation capabilities. Finally, multi-scale features were applied for prediction. Results: A public data set of 14,236 hand radiographs, provided by the Radiological Society of North America (RSNA), was used to develop and validate 2M-Net. In the public benchmark testing, the mean absolute error (MAE) between the bone age estimates of the model and of the reviewer was 3.98 months (3.89 months for males and 4.07 months for females). Conclusions: By using the jigsaw method to construct a multi-task learning strategy and inserting the self-attention module for efficient global modeling, we established 2M-Net, which is comparable to the previous best method in terms of performance.

Optimizing treatment sequence for inoperable locally advanced breast cancer: Long-term outcomes of surgery first versus neoadjuvant chemotherapy in a real-world setting.

Locally advanced breast cancer (LABC) is challenging with limited treatment options. This study investigates the feasibility and long-term outcomes of upfront surgery compared to neoadjuvant chemotherapy (NAC) in a real-world cohort. This retrospective study analyzed 243 inoperable LABC patients (excluding T3N1M0) that underwent upfront surgery (n = 187) or NAC (n = 56) in matched groups. Disease-free survival (DFS) and overall survival (OS) are primary outcomes. Secondary outcomes included NAC response rate and subgroup analyses based on age, tumor stage, and treatment response. Survival was estimated using Kaplan-Meier methods with log-rank tests for comparisons. Cox proportional hazards models were used for subgroup analyses. With a median follow-up of 60.9 months, no significant difference emerged in 5-year OS (upfront surgery: 89.6%, NAC: 81.9%, p = .12) or 5-year DFS rates (73.0% vs. 67.1%, p = .24). Subgroup analyses revealed upfront surgery offered significantly better OS for patients under 60 (HR = 0.32; 95% CI: 0.10-0.96; p = .0429) and stage IIIA disease (HR = 0.22; CI: 0.06-0.86; p = .03). Upfront surgery showed a trend towards improved OS for tumors under 5 cm (HR = 0.37; 95% CI: 0.13-1.03; p = .056). Patients with progressive disease (PD) or stable disease (SD) after NAC had significantly worse DFS (HR = 0.27; 95% CI: 0.09-0.79; p = .017) and OS (HR = 0.09; 95% CI: 0.02-0.48; p = .004) compared to responders. Upfront surgery may be viable for LABC patients, particularly younger patients, those with stage IIIA disease, or smaller tumors. NAC response can inform treatment decisions. These findings highlight the need for personalized LABC treatment considering patient characteristics and NAC response.

Regulatory mechanism of strigolactone in tall fescue to low-light stress.

Strigolactone (SL), a plant hormone derived from carotenoids, has been recognized for its pivotal role in regulating plant growth. Nevertheless, the influence of SL on tall fescue (Festuca arundinacea) under low-light conditions remains unclear. This study aimed to investigate the impact of SL on various aspects of tall fescue, including its morphological characteristics, photosynthesis, levels of antioxidant and concentrations of SL, under low light intensity (LI). The findings showed that GR24, an artificial analog of SL, positively influenced several parameters of tall fescue under LI. In particular, it enhanced the morphological features such as plant height, leaf width, and biomass, while reducing the number of tillers. Furthermore, it improved the efficiency of photosynthetic by enhancing chlorophyll fluorescence and the gas exchange parameters, mitigating cell damage and improving the contents of antioxidants by increasing the levels of antioxidant enzymes and non-enzymatic antioxidant compounds. Moreover, treatment with SL led to elevated concentrations of this hormone and the levels of gene expression in related pathways. Owing to the immaturity of the genetic transformation system in tall fescue, partial validation through transgenic and mutant materials was obtained using Arabidopsis (Arabidopsis thaliana). These findings demonstrate that SL alleviates the physiological indicators of tall fescue under LI stress and enhances its tolerance to shade. Additionally, it suggests that SL may regulate the shade tolerance of tall fescue through the involvement of FaD14.

Efficacy and safety of second-line therapies for advanced hepatocellular carcinoma: a network meta-analysis of randomized controlled trials.

BACKGROUND: The selection of appropriate second-line therapy for liver cancer after first-line treatment failure poses a significant clinical challenge due to the lack of direct comparative studies and standard treatment protocols. A network meta-analysis (NMA) provides a robust method to systematically evaluate the clinical outcomes and adverse effects of various second-line treatments for hepatocellular carcinoma (HCC). METHODS: We systematically searched PubMed, Embase, Web of Science and the Cochrane Library to identify phase III/IV randomized controlled trials (RCTs) published up to March 11, 2024. The outcomes extracted were median overall survival (OS), median progression-free survival (PFS), time to disease progression (TTP), disease control rate (DCR), objective response rate (ORR), and adverse reactions. This study was registered in the Prospective Register of Systematic Reviews (CRD42023427843) to ensure transparency, novelty, and reliability. RESULTS: We included 16 RCTs involving 7,005 patients and 10 second-line treatments. For advanced HCC patients, regorafenib (HR = 0.62, 95%CI: 0.53-0.73) and cabozantinib (HR = 0.74, 95%CI: 0.63-0.85) provided the best OS benefits compared to placebo. Cabozantinib (HR = 0.42, 95%CI: 0.32-0.55) and regorafenib (HR = 0.46, 95% CI: 0.31-0.68) also offered the most significant PFS benefits. For TTP, apatinib (HR = 0.43, 95% CI: 0.33-0.57), ramucirumab (HR = 0.44, 95% CI: 0.34-0.57), and regorafenib (HR = 0.44, 95% CI: 0.38-0.51) showed significant benefits over placebo. Regarding ORR, ramucirumab (OR = 9.90, 95% CI: 3.40-42.98) and S-1 (OR = 8.68, 95% CI: 1.4-154.68) showed the most significant increases over placebo. Apatinib (OR = 3.88, 95% CI: 2.48-6.10) and cabozantinib (OR = 3.53, 95% CI: 2.54-4.90) provided the best DCR benefits compared to placebo. Tivantinib showed the most significant advantages in terms of three different safety outcome measures. CONCLUSIONS: Our findings suggest that, in terms of overall efficacy and safety, regorafenib and cabozantinib are the optimal second-line treatment options for patients with advanced HCC.

The Effects of Daily-Living Risks on Breast Cancer-Related Lymphedema.

BACKGROUND: Conventional advice to reduce the risk of breast cancer-related lymphedema (BCLE) suggests avoidance of daily-living risks, and limited research has investigated these risks. OBJECTIVE: This study aimed to examine the occurrence, patterns, and effects of daily-living risks on BCLE. METHODS: A cross-sectional design was used to collect data from 567 patients at a metropolitan cancer center in the United States. The Lymphedema Risk-Reduction Behavior Checklist was used to assess the occurrence of 11 daily-living risks. Descriptive, regression, and factor analyses were performed. RESULTS: Significant odds of BCLE were associated with infection (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.95-3.42), cuts/scratches (OR 2.65, 95% CI 1.97-3.56), sunburn (OR 1.89, 95% CI 1.39-3.56), oil splash or steam burns (OR 2.08, 95% CI 1.53-3.83), and insect bites (OR 1.59, 95% CI 1.18-2.13). The daily-living risks were clustered into factors related to skin trauma and carrying objects. Skin trauma risk was significantly associated with BCLE (B = 0.539, z = 3.926, OR 1.714, 95% CI 1.312-2.250; p < 0.001). Having three, four, or five skin trauma risks significantly increased the odds of BCLE to 4.31, 5.14, and 6.94 times, respectively. The risk of carrying objects had no significant or incremental effects on BCLE. CONCLUSION: Complete avoidance of daily-living risks is challenging given 52.73% of patients incurred more than five daily-living risks. Our study findings underscore the importance of 'what to do' strategies to minimize infection and skin trauma.

Acquired methemoglobinemia in a third trimester puerpera and her premature infant with sodium nitrite poisoning: A case report.

BACKGROUND: The common cause of sodium nitrite poisoning has shifted from previous accidental intoxication by exposure or ingestion of contaminated water and food to recent alarming intentional intoxication as an employed method of suicide/exit. The subsequent formation of methemoglobin (MetHb) restricts oxygen transport and utilization in the body, resulting in functional hypoxia at the tissue level. In clinical practice, a mismatch of cyanotic appearance and oxygen partial pressure usually contributes to the identification of methemoglobinemia. Prompt recognition of characteristic mismatch and accurate diagnosis of sodium nitrite poisoning are prerequisites for the implementation of standardized systemic interventions. CASE SUMMARY: A pregnant woman was admitted to the Department of Critical Care Medicine at the First Affiliated Hospital of Harbin Medical University due to consciousness disorders and drowsiness 2 h before admission. Subsequently, she developed vomiting and cyanotic skin. The woman underwent orotracheal intubation, invasive mechanical ventilation (IMV), and correction of internal environment disturbance in the ICU. Her premature infant was born with a higher-than-normal MetHb level of 3.3%, and received detoxification with methylene blue and vitamin C, supplemental vitamin K1, an infusion of fresh frozen plasma, as well as respiratory support via orotracheal intubation and IMV. On day 3 after admission, the puerpera regained consciousness, evacuated the IMV, and resumed enteral nutrition. She was then transferred to the maternity ward 24 h later. On day 7 after admission, the woman recovered and was discharged without any sequelae. CONCLUSION: MetHb can cross through the placental barrier. Level of MetHb both reflects severity of the sodium nitrite poisoning and serves as feedback on therapeutic effectiveness.

Metalenses phase characterization by multi-distance phase retrieval.

Metalens, characterized by their unique functions and distinctive physical properties, have gained significant attention for their potential applications. To further optimize the performance of metalens, it is necessary to characterize the phase modulation of the metalens. In this study, we present a multi-distance phase retrieval system based on optical field scanning and discuss its convergence and robustness. Our findings indicate that the system is capable of retrieving the phase distribution of the metalens as long as the measurement noise is low and the total length of the scanned light field is sufficiently long. This system enables the analysis of focal length and aberration by utilizing the computed phase distribution. We extend our investigation to measure the phase distribution of the metalens operating in the near-infrared (NIR) spectrum and identify the impact of defects in the sample on the phase. Additionally, we conduct a comparative analysis of the phase distribution of the metalens in air and ethanol and observe the variations in the phase modulation of the metalens in different working mediums. Our system provides a straightforward method for the phase characterization of metalens, aiding in optimizing the metalens design and functionality.

Innovative indenone-derivative colorimetric fluorescent probe: A approach for copper ion detection in water.

Copper (Cu2+) is a metal chemical element closely related to human life and is widely used in many fields. However, with the discharge of copper wastewater, the water quality will be seriously affected, leading to excessive intake of Cu2+ and a variety of diseases. Hence, there is a pressing need for an effective detection method for Cu2+ in aqueous environments. Leveraging the remarkable attributes of GFP chromophores and indenone derivatives, we have created a novel colorimetric fluorescent probe P-Cu2+, tailored for efficient copper ion detection. The addition of Cu2+ causes the solution to visibly change from colorless to a pronounced yellow, enabling naked-eye detection and offering promise for real sample analysis.

A photoluminescent hydrogen-bonded biomass aerogel for sustainable radiative cooling.

Passive radiant cooling is a potentially sustainable thermal management strategy amid escalating global climate change. However, petrochemical-derived cooling materials often face efficiency challenges owing to the absorption of sunlight. We present an intrinsic photoluminescent biomass aerogel, which has a visible light reflectance exceeding 100%, that yields a large cooling effect. We discovered that DNA and gelatin aggregation into an ordered layered aerogel achieves a solar-weighted reflectance of 104.0% in visible light regions through fluorescence and phosphorescence. The cooling effect can reduce ambient temperatures by 16.0°C under high solar irradiance. In addition, the aerogel, efficiently produced at scale through water-welding, displays high reparability, recyclability, and biodegradability, completing an environmentally conscious life cycle. This biomass photoluminescence material is another tool for designing next-generation sustainable cooling materials.

Label-Free Detection of DNA Base Mutation and Hybridized DNA by an Electrostatically Modified 3D Plasmonic Array.

Surface-enhanced Raman scattering (SERS) represents a promising avenue for DNA detection as it offers intrinsic chemical insights with high sensitivity compared to conventional methods. However, label-free and quantitative detection of unmodified DNA by SERS remains a major challenge in DNA analysis. To overcome this challenge, we propose a positively charged plasmonic nanosurface for DNA capture and quantitative analysis. Highly sensitive and uniform SERS enhancement was realized by a three-dimensional plasmonic array supporting well-designed hybrid plasmonic modes. Subsequently, the plasmonic array was modified with an electrostatically functionalized PDDA (poly(diene-dimethylammonium-chloride)) self-assembled monolayer in a single step. The effectiveness of the resulting PDDA-SERS substrate was demonstrated by the label-free and quantitative detection of base content and base mutation in hybridized DNA. The PDDA-SERS substrate provides a robust platform for SERS analysis not only of DNA but also of other electronegative analytes.

Lignin-assisted electronic modulation on NiSe/FeOx heterointerface for boosting electrocatalytic oxygen evolution reaction.

The development of productive and durable non-precious metal catalysts for the sluggish oxygen evolution reaction (OER) is critical for water splitting. Herein, a novel NiSe-FeOx heterojunction encapsulated in lignin-derived carbon layer (NiSe-FeOx@LC) was synthesized via hydrothermal self-assembly and in-situ pyrolysis. NiSe-FeOx@LC exhibited excellent OER performance with an overpotential of 265 mV at 50 mA·cm-2, a Tafel slope of 83 mV·dec-1, as well as long-term stability. Both experimental and DFT calculation results indicated that the doping of FeOx into NiSe@LC successfully optimized the dual interface structure between NiSe and FeOx, thereby promoted the d-bands orbital hybridization, that facilitated electron transfer. Besides, the carbon coating effectively protected the NiSe-FeOx components from leaching and agglomerating during the reaction. This study provides insight into the significance of lignin-derived carbon-encapsulated metallic catalyst for electrocatalytic OER process.

Development of a 1-step multiplex PCR assay for the detection of S. Enteritidis, S. Pullorum, S. Typhimurium, and S. Infantis associated with poultry production.

Salmonellosis in poultry is detrimental to the advancement of the breeding industry and poses hazards to human health. Approximately 2,600 Salmonella varieties exist, among which S. Enteritidis, S. Pullorum, S. Typhimurium, and S. Infantis are prevalent serotypes in the poultry industry in recent years. They can also infect humans by contaminating poultry eggs and meat. Therefore, identifying these serotypes is crucial for successful preventive and control interventions. The White-Kauffmann-Le Minor scheme is time-consuming and requires expensive reagents. Whole-genome sequencing (WGS) and other molecular biology techniques require skilled technical staff. In comparison, the polymerase chain reaction (PCR) is more accurate, rapid, and inexpensive, thus proving suitable for widespread application in the poultry industry. Here, we selected 4 specific primers: lygD, mdh, ipaJ, and SIN_02055, which correspond to detecting S. Enteritidis, S. Typhimurium, S. Pullorum, and S. Infantis, respectively. They were integrated into a 1-step multiplex PCR method. We optimized the PCR method by utilizing specificity test results to determine the optimal annealing temperature (57°C). The PCR method exhibited excellent sensitivity for genomic DNA and bacterial cultures. We used the developed method to determine 157 clinical Salmonella isolates from various stages of the poultry production chain. The results aligned with serotype data generated via WGS analysis, demonstrating the method's excellent accuracy. In conclusion, this study developed a 1-step multiplex PCR method that simultaneously identifies S. Enteritidis, S. Typhimurium, S. Pullorum, and S. Infantis, allowing routine mass detection in the grass-root poultry industry.

Quantum Molecular Docking with a Quantum-Inspired Algorithm.

Molecular docking (MD) is a crucial task in drug design, which predicts the position, orientation, and conformation of the ligand when it is bound to a target protein. It can be interpreted as a combinatorial optimization problem, where quantum annealing (QA) has shown a promising advantage for solving combinatorial optimization. In this work, we propose a novel quantum molecular docking (QMD) approach based on a QA-inspired algorithm. We construct two binary encoding methods to efficiently discretize the degrees of freedom with an exponentially reduced number of bits and propose a smoothing filter to rescale the rugged objective function. We propose a new quantum-inspired algorithm, hopscotch simulated bifurcation (hSB), showing great advantages in optimizing over extremely rugged energy landscapes. This hSB can be applied to any formulation of an objective function under binary variables. An adaptive local continuous search is also introduced for further optimization of the discretized solution from hSB. Concerning the stability of docking, we propose a perturbation detection method to help rank the candidate poses. We demonstrate our approach on a typical data set. QMD has shown advantages over the search-based Autodock Vina and the deep-learning DIFFDOCK in both redocking and self-docking scenarios. These results indicate that quantum-inspired algorithms can be applied to solve practical problems in drug discovery even before quantum hardware become mature.

Transcriptome-wide m6A methylation profile reveals tissue specific regulatory networks in switchgrass (Panicum virgatum L.) under cadmium stress.

The heavy metal cadmium (Cd), known for its high toxicity, poses a grave threat to human health through the food chain. N6-methyladenosine (m6A), the most abundant internal modification, regulates plant adaptation to various adversities, yet the panorama of m6A modifications in switchgrass under cadmium stress remains elusive. This study examines the physiological responses of switchgrass roots and shoots exposed to 50 µM CdCl2, alongside an overview of transcriptome-wide m6A methylation patterns. After cadmium treatment, methylation modifications are primarily enriched near stop codons and the 3'UTR region, with a negative correlation between m6A modification and gene expression levels. In shoots, approximately 58 % of DEGs with m6A modifications show upregulation in expression and decrease in m6A peaks, including zinc transporter 4-like (ZIP4). In roots, about 43 % of DEGs with m6A modifications exhibit downregulation in expression and increase in m6A peaks, such as the ABC transporter family member (ABCG25). We further validate the m6A enrichment, gene expression and mRNA stability of ZIP4 in response to Cd treatment. The results suggest that the negative correlation of m6A enrichment and gene expression is due to altered mRNA stability. Our study establishes an m6A regulatory network governing cadmium transport in switchgrass roots and shoots, offering new avenues for candidate gene manipulation in phytoremediation applications of heavy metal pollution.

Rapid Release of Silicon by Ultrafast Joule Heating Generates Mechanically Stable Shell-Shell Si/C Anodes with Dominant Inward Deformation.

As a promising anode material, silicon-carbon composites encounter great challenges related to internal stress release and contact between the composites during lithiation. These issues lead to material degradation and concomitantly rapid capacity decline. Here, we report a type of shell-shell silicon-carbon (SS-Si/C) composite, which consists of a carbon shell tightly coated with a silicon shell. The mechanical analysis unveils that the dominant inward expansion of the Si shell is achieved through the synergistic effect of the outer carbon shell and the inner hollow structure. Benefiting from the well-tailored shell-shell structure, the SS-Si/C anode exhibits exceptional performance, boasting a high specific capacity (1690.3 mA h g-1 after 550 cycles at 0.5 A g-1), a high areal capacity (2.05 mA h cm-2 after more than 400 cycles at 0.5 mA cm-2), and an extended cycling life (1055.6 mA h g-1 after 1000 cycles at 8 A g-1), far exceeding commercially available Si/C anodes. Using the well-designed SS-Si/C anode, full cells assembled with LiCoO2 (LCO) or LiFePO4 (LFP) cathodes achieve favorable rate capability and cyclic stability. Notably, at a high rate of 6 C (1 C = 170 and 270 mA g-1 for LFP and LCO, respectively), these full cells deliver high specific capacities of 79.5 mA h g-1 and 64.9 mA h g-1 when using LCO and LFP, respectively, demonstrating the potential of SS-Si/C anodes for practical applications. The straightforward and safe synthesis method in this work enables the rational design of hollow structures with distinct properties.

Efficient molecular conformation generation with quantum-inspired algorithm.

CONTEXT: Conformation generation, also known as molecular unfolding (MU), is a crucial step in structure-based drug design, remaining a challenging combinatorial optimization problem. Quantum annealing (QA) has shown great potential for solving certain combinatorial optimization problems over traditional classical methods such as simulated annealing (SA). However, a recent study showed that a 2000-qubit QA hardware was still unable to outperform SA for the MU problem. Here, we propose the use of quantum-inspired algorithm to solve the MU problem, in order to go beyond traditional SA. We introduce a highly compact phase encoding method which can exponentially reduce the representation space, compared with the previous one-hot encoding method. For benchmarking, we tested this new approach on the public QM9 dataset generated by density functional theory (DFT). The root-mean-square deviation between the conformation determined by our approach and DFT is negligible (less than about 0.5Å), which underpins the validity of our approach. Furthermore, the median time-to-target metric can be reduced by a factor of five compared to SA. Additionally, we demonstrate a simulation experiment by MindQuantum using quantum approximate optimization algorithm (QAOA) to reach optimal results. These results indicate that quantum-inspired algorithms can be applied to solve practical problems even before quantum hardware becomes mature. METHODS: The objective function of MU is defined as the sum of all internal distances between atoms in the molecule, which is a high-order unconstrained binary optimization (HUBO) problem. The degree of freedom of variables is discretized and encoded with binary variables by the phase encoding method. We employ the quantum-inspired simulated bifurcation algorithm for optimization. The public QM9 dataset is generated by DFT. The simulation experiment of quantum computation is implemented by MindQuantum using QAOA.

The Effect of Local Application of Tea Tree Oil Adjunctive to Daily Oral Maintenance and Nonsurgical Periodontal Treatment: A Systematic Review and Meta-Analysis of Randomised Controlled Studies.

PURPOSE: To evaluate the efficacy of the adjunctive use of tea tree oil (TTO) for dental plaque control and nonsurgical periodontal treatment (NSPT). MATERIALS AND METHODS: Three electronic databases were searched from 2003. The reference lists of the included articles and relevant reviews were also manually searched. Randomised controlled trials reporting the clinical outcomes of the topical use of TTO as an adjunct to daily oral hygiene or scaling and root planing (SRP) were included. Regarding the use of TTO as an adjunctive to daily oral hygiene, the primary outcome was plaque index (PI) reduction. Regarding the use of TTO as an adjunctive to SRP, probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain were the primary outcomes. The secondary outcomes were adverse events. RESULTS: Eleven studies were included for qualitative analysis, 9 studies were included for quantitative analysis, and 6 studies were included to examine the application of TTO mouthwash as an adjunctive to daily oral hygiene. In addition, three studies were included to analyse the subgingival use of TTO adjunctive to SRP at selected sites. The results indicated a nonsignificant improvement in PI reduction in the TTO mouthwash group compared with placebo. The incidence of adverse events was statistically significantly greater in the CHX group than in the TTO group. For subgingival use of TTO adjunctive to SRP, beneficial effects were observed in the TTO group compared with SRP alone in terms of PPD and CAL at both three and six months post-treatment. However, an unpleasant taste was reported in three out of four studies. CONCLUSION: There is a lack of strong evidence to support the beneficial effects of TTO. Studies with larger sample sizes and standardised evaluation criteria are needed to further demonstrate the clinical relevance of TTO.

Liguzinediol potentiates the metabolic remodeling by activating the AMPK/SIRT3 pathway and represses Caspase-3/GSDME-mediated pyroptosis to ameliorate cardiotoxicity.

BACKGROUND: Liguzinediol (Lig) has emerged as a promising candidate for mitigating Doxorubicin (DOX)-induced cardiotoxicity, a significant limitation in the clinical application of this widely used antineoplastic drug known for its efficacy. This study aimed to explore the effects and potential mechanisms underlying Lig's protective role against DOX-induced cardiotoxicity. METHODS: C57BL/6 mice were treated with DOX. Cardiac function changes were observed by echocardiography. Cardiac structure changes were observed by HE and Masson staining. Immunofluorescence was applied to visualize the cardiomyocyte apoptosis. Western blotting was used to detect the expression levels of AMP-activated protein kinase (AMPK), sirtuin 3 (SIRT3), Caspase-3 and gasdermin E N-terminal fragment (GSDME-N). These experiments confirmed that Lig had an ameliorative effect on DOX-induced cardiotoxicity in mice. RESULTS: The results demonstrated that Lig effectively countered myocardial oxidative stress by modulating intracellular levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Lig reduced levels of creatine kinase (CK) and lactate dehydrogenase (LDH), while ameliorating histopathological changes and improving electrocardiogram profiles in vivo. Furthermore, the study revealed that Lig activated the AMPK/SIRT3 pathway, thereby enhancing mitochondrial function and attenuating myocardial cell apoptosis. In experiments with H9C2 cells treated with DOX, co-administration of the AMPK inhibitor compound C (CC) led to a significant increase in intracellular ROS levels. Lig intervention reversed these effects, along with the downregulation of GSDME-N, interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), suggesting a potential role of Lig in mitigating Caspase-3/GSDME-mediated pyroptosis. CONCLUSION: The findings of this study suggest that Lig effectively alleviates DOX-induced cardiotoxicity through the activation of the AMPK/SIRT3 pathway, thereby presenting itself as a natural product with therapeutic potential for preventing DOX-associated cardiotoxicity. This novel approach may pave the way for the development of alternative strategies in the clinical management of DOX-induced cardiac complications.

Bioactive Patch for Rotator Cuff Repairing via Enhancing Tendon-to-Bone Healing: A Large Animal Study and Short-Term Outcome of a Clinical Trial.

Tissue engineering has demonstrated its efficacy in promoting tissue regeneration, and extensive research has explored its application in rotator cuff (RC) tears. However, there remains a paucity of research translating from bench to clinic. A key challenge in RC repair is the healing of tendon-bone interface (TBI), for which bioactive materials suitable for interface repair are still lacking. The umbilical cord (UC), which serves as a vital repository of bioactive components in nature, is emerging as an important source of tissue engineering materials. A minimally manipulated approach is used to fabricate UC scaffolds that retain a wealth of bioactive components and cytokines. The scaffold demonstrates the ability to modulate the TBI healing microenvironment by facilitating cell proliferation, migration, suppressing inflammation, and inducing chondrogenic differentiation. This foundation sets the stage for in vivo validation and clinical translation. Following implantation of UC scaffolds in the canine model, comprehensive assessments, including MRI and histological analysis confirm their efficacy in inducing TBI reconstruction. Encouraging short-term clinical results further suggest the ability of UC scaffolds to effectively enhance RC repair. This investigation explores the mechanisms underlying the promotion of TBI repair by UC scaffolds, providing key insights for clinical application and translational research.